MANGANESE (III) BASED OXIDATIVE FREE RADICAL CYCLIZATION

锰 (III) 基氧化自由基环化

基本信息

批准号：
6221444
负责人：
BARRY B. SNIDER
金额：
$ 6.38万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-08-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6221444
关键词：
antibiotics carbonyl compound chemical synthesis cyclization diterpenes free radicals hepatotoxin ketones manganese stereochemistry stereoisomer

项目摘要

DESCRIPTION: Oxidative free-radical cyclizations, in which the initial radical is generated oxidatively, and/or the cyclic radical is oxidized to terminate the reaction, have considerable synthetic potential since more highly functionalized products can be prepared from simpler precursors than with the standard tin hydride reductive radical cyclizations. The goal of this research is to develop oxidative free- radical cyclization into a reliable and versatile method for the synthesis of highly functionalized cyclic and polycyclic compounds. The PI's studies over the past ten years have shown that this will be a valuable synthetic method for formation of radicals from 1,3-dicarbonyl compounds and related acidic substrates. The PI has recently discovered that high yields of cyclic products can be obtained from monocarbonyl compounds at minus 80 oC under some circumstances. Preliminary results suggest that high yields are obtained from ketones in which enolization is possible or favored to only one side of the ketone and when the product can't enolize thereby preventing further oxidation of the product. Oxidative cyclizations of a conjugated enone and an aldehyde containing an unsaturated side chain also proceed in good yield. The PI wishes to fully explore and develop the scope of these reactions. Since these starting materials are very simple, the oxidative cyclization of monocarbonyl compounds should have even broader scope and utility in synthesis than those of 1,3-dicarbonyl compounds. The focus of the oxidative free radical cyclization project is the development of new synthetic methodology that will be broadly applicable in the synthesis of wide variety of biologically active compounds. The PI plans to use oxidative free-radical cyclizations for short syntheses of gymnomitrol and upial. In both cases the syntheses are designed to demonstrate the potential utility of this reaction by the simple synthesis of a moderately complex natural product. The gymnomitrol synthesis requires only three steps from a previously prepared intermediate. The upial synthesis utilizes oxidative cyclization to convert a readily available cyclohexane-1,3-dione to a complex bicyclic dione. The antibiotic diterpenes cyathin B3, allocyathin B2 and the nerve growth factor production stimulant erinacine A will be prepared by efficient, stereospecific syntheses using a Lewis acid catalyzed ene reaction to give a tricyclic dienol containing the complete carbon skeleton, proper stereochemistry and suitable functionality for completion of the syntheses. The structurally novel, potent hepatotoxin cylindrospermopsin will be synthesized by the addition of ammonia to a dienone, condensation of the resulting diamine with a thiourea derivative, and epoxide opening to construct the ticyclic guanidinium core of cylindrospermopsin with control of all but one of the 6 stereo centers.

描述：氧化自由基环化学，其中最初自由基是氧化产生的，并且/或环状自由基被氧化。终止反应，具有相当大的合成潜力可以从更简单的前体比标准锡氢化物还原自由基环化。这项研究的目的是发展氧化自由 - 从根本上循环成一种可靠且通用的方法高度功能化的循环和多环化合物的合成。这 Pi在过去十年中的研究表明，这将是从1,3-二骨的自由基形成的有价值的合成方法化合物和相关的酸性底物。 PI最近发现了可以从单碳邻苯甲中获得高产物的高产在某些情况下，减去80 OC的化合物。初步结果表明高产量是从酮的酮中获得的可能或仅偏爱酮的一侧，何时产品无法耐燃料，从而防止进一步氧化产品。共轭烯酮和醛的氧化环化包含一个不饱和侧链也以良好的收率进行。这 PI希望充分探索和发展这些反应的范围。由于这些起始材料非常简单，因此氧化单一碳酸盐化合物的环化应具有更大的范围，并且合成中的效用比1,3-二碳酮化合物的效用。重点氧化自由基环化项目的发展是新的合成方法将广泛适用于多种生物活性化合物的合成。 PI计划使用氧化自由基环化进行短合成体操和外向。在这两种情况下，合成均设计为通过简单证明了这种反应的潜在效用中等复杂的天然产物的合成。体操运动物合成仅需要三个步骤中间的。 Upial合成利用氧化环化为将易于使用的环己烷1,3-二酮转换为复杂的双环 Dione。抗生素二酸囊蛋白B3，分析B2和神经生长因子产生兴奋剂Erinacine A将准备通过有效的立体特异性合成，使用刘易斯酸催化的ENE 给出包含完整碳的三环二烯的反应骨架，适当的立体化学和适当的功能完成合成。结构新颖的，有效的肝毒素通过在A中添加氨 Dienone，与Thiourea的最终二胺的凝结衍生物和环氧化物开口，以构建ticyclic鸟阵除6个立体声之一以外的所有人的核蛋白核心核心核心素中心。